| 1. |
|
|
| 2. |
|
|
| 3. |
- Correa, Fernando, et al.
(author)
-
The Nrf2-inducible antioxidant defense in astrocytes can be both up- and down-regulated by activated microglia:Involvement of p38 MAPK.
- 2011
-
In: Glia. - : Wiley. - 1098-1136 .- 0894-1491. ; 59:5, s. 785-99
-
Journal article (peer-reviewed)abstract
- The effects of microglia-conditioned medium (MCM) on the inducible Nrf2 system in astrocyte-rich cultures were investigated by determination of glutathione (GSH) levels, γglutamylcysteine ligase (γGCL) activity, the protein levels of Nrf2, Keap1, the modulatory subunit of γGCL (γGCL-M) and activated MAP kinases (ERK1/2, JNK and p38). Microglia were either cultured for 24 h in serum-free culture medium to achieve microglia-conditioned medium from non-activated cells (MCM(0) ), used as control condition, or activated with different concentrations (0.1-1,000 ng mL(-1) ) of lipopolysaccharide (LPS) to produce MCM(0.1-1,000) . Acute exposure (24 h) to MCM(100) increased GSH, γGCL activity, the protein levels of γGCL-M, Nrf2, and activated JNK and ERK1/2 in astrocyte-rich cultures. In contrast, treatment with MCM(10) for 24 h decreased components of the Nrf2 system in parallel with activation of p38 MAPK. Stimulation of the Nrf2 system by tBHQ was partly intact after 24 h but blocked after 72 h treatment with MCM(10) and MCM(100) . This down-regulation after 72 h correlated with activation of p38 MAPK and lack of ERK1/2 and JNK activation. The negative effects were partly reversed by an inhibitor of p38 which restored tBHQ mediated protection against oxidative stress. In conclusion, the study showed a negative effect of MCM(10) on the inducible anti-oxidant defense in astrocyte-rich cultures at both 24 and 72 h that correlated with activation of p38 and was partly reversed by a p38 inhibitor. A transient protective effect of MCM(100) on astrocyte-rich cultures against H(2)O(2) toxicity was observed at 24 h which coincided with activation of JNK and ERK1/2.
|
|
| 4. |
- Correa, Fernando, et al.
(author)
-
Time-Dependent Effects of Systemic Lipopolysaccharide Injection on Regulators of Antioxidant Defence Nrf2 and PGC-1α in the Neonatal Rat Brain.
- 2013
-
In: Neuroimmunomodulation. - : S. Karger AG. - 1423-0216 .- 1021-7401. ; 20:4, s. 185-193
-
Journal article (peer-reviewed)abstract
- Background/Aims: Both excitotoxicity and neuroinflammation are associated with oxidative stress. One transcription factor, nuclear factor E2-related factor 2 (Nrf2), and one transcription cofactor, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), increase the endogenous antioxidant defence and can thus modulate neuronal cell death. Here, we investigated the temporal effects (after 24 and 72 h) of systemic (i.p.) administration of lipopolysaccharide (LPS) on the cerebral Nrf2 and PGC-1α systems. Methods and Results: Seven-day-old rat pups were injected with LPS (0.3 mg/kg). After 24 h, the protein levels of γ-glutamylcysteine ligase modulatory subunit, γ-glutamylcysteine ligase catalytic subunit, Nrf2, PGC-1α and manganese superoxide dismutase (MnSOD) were increased in parallel with decreased levels of Keap1. These effects were correlated with an increased level of phosphorylated Akt and elevated acetylation of histone 4. In contrast, 72 h following LPS, a decrease in the components of the Nrf2 system in parallel with an increase in Keap1 was observed. The down-regulation after 72 h correlated with phosphorylation of p38 mitogen-activated protein kinase, while there were no changes in PGC-1α and MnSOD protein levels or the acetylation/methylation pattern of histones. Conclusion: Systemic LPS in neonatal rats induced time-dependent changes in brain Nrf2 and PGC-1α that correlated well with the protective effect observed after 24 h (pre-conditioning) and the deleterious effects observed after 72 h (sensitizing) of systemic LPS reported earlier. Collectively, the results point towards Nrf2 and PGC-1α as a possible mechanism behind these effects.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Rydgren, Tobias, et al.
(author)
-
Administration of IL-1 Trap prolongs survival of transplanted pancreatic islets to type 1 diabetic NOD mice
- 2013
-
In: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 63:2, s. 123-129
-
Journal article (peer-reviewed)abstract
- We previously reported that IL-1 Trap (a hybrid molecule consisting of the extracellular domain of IL-1 receptor accessory protein and IL-1 receptor type 1 arranged inline and fused to the Fc-portion of IgG1) can protect rat pancreatic islets in vitro against noxious effects induced by IL-1 beta. In this study we tested the effect of administration of a murine IL-1 Trap on the recurrence of disease (ROD) model in non-obese diabetic (NOD) mice. Spontaneously diabetic female NOD mice received implantation of a curative number (600) of syngeneic pancreatic islets beneath their left kidney capsule from young healthy NOD mouse donors. Once a day, the mice were injected subcutaneously with IL-1 Trap (30 mg/kg bodyweight), or an equimolar dose Fc-control protein (8.4 mg/kg bodyweight) or saline. The treatments were maintained until ROD (i.e. a blood glucose value >= 11.1 mM for 2 consecutive days) or until 5 days after transplantation. 3 out of 11 mice treated with IL-1 Trap showed a significantly increased graft survival compared to all other mice, and analysis of relative cytokine mRNA levels in isolated spleen cells showed elevated IL-4 mRNA levels, but no differences in FoxP3 or iNOS staining of grafts, from mice treated with IL-1 Trap, at both endpoints, compared to both control groups. Administration of IL-1 Trap counteracts islet cell destruction in the NOD mouse model of type 1 diabetes. In part this could be due to a shift towards Th2 cytokine production seen in IL-1 Trap treated animals.
|
|
| 8. |
- Taube, Elin, et al.
(author)
-
Loneliness and health care consumption among older people
- 2014
-
In: Scandinavian Journal of Caring Sciences. - : John Wiley & Sons. - 0283-9318 .- 1471-6712. ; 29:3, s. 435-443
-
Journal article (peer-reviewed)abstract
- Few studies have investigated loneliness in relation to health care consumption among frail older people. The aim of this study was to examine loneliness, health-related quality of life (HRQoL), and health complaints in relation to health care consumption of in- and outpatient care among frail older people living at home. The study, with a cross-sectional design, comprised a sample of 153 respondents aged from 65 years (mean age 81.5 years) or older, who lived at home and were frail. Data was collected utilising structured interviews in the respondent's home assessing demographic data, loneliness, HRQoL and health complaints. Patient administrative registers were used to collect data on health care consumption. Loneliness was the dependent variable in the majority of the analyses and dichotomised. For group comparisons Student′s t-test, Mann–Whitney U-test and Chi-square test were used. The results showed that 60% of the respondents had experienced loneliness during the previous year, at least occasionally. The study identified that lonely respondents had a lower HRQoL (p = 0.022), with a higher total number of reported health complaints (p = 0.001), and used more outpatient services including more acute visits at the emergency department, compared to not lonely respondents (p = 0.026). Multiple linear regression analysis showed that a depressed mood was independently associated to total use of outpatient care (B = 7.4, p < 0.001). Therefore, it might not be loneliness, per se, that is the reason for seeking health care. However, reasons for using health care services are difficult to determine due to the complex situation for the frail older person. To avoid emergency department visits and to benefit the well-being of the frail older person, interventions targeting the complex health situation, including loneliness, are suggested.
|
|
